The global incidence of depression is progressively on the rise and tends to occur more in younger generations,however the pathogenesis of the disease is unclear.Meanwhile,epigenetics is a modification which produces ...The global incidence of depression is progressively on the rise and tends to occur more in younger generations,however the pathogenesis of the disease is unclear.Meanwhile,epigenetics is a modification which produces heritable alterations in the DNA sequence,which ultimately manifest in phenotypic differences.It has been suggested that the onset and development of depression can be tentatively explained by the combination of epigenetic and environmental factors.This paper reviews epigenetic changes in depression in the context of environmental factors,including DNA methylation modifications,histone modifications,and non-coding RNA regulation.An epigenetic-based therapeutic outlook was also proposed in this paper,which initially elucidates the epigenetic mechanisms underlying the pathogenesis of depressions and provides a theoretical basis for the treatment of depression.展开更多
Dynamic regulation and packaging of genetic information is achieved by the organization of DNA into chromatin. Nucleosomal core histones, which form the basic repeating unit of chromatin, are subject to various post-t...Dynamic regulation and packaging of genetic information is achieved by the organization of DNA into chromatin. Nucleosomal core histones, which form the basic repeating unit of chromatin, are subject to various post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitinylation. These modifications have effects on chromatin structure and, along with DNA methylation, regulate gene transcription.The goal of this study was to determine if patterns in modifications were related to different categories of genomic features, and, if so, if the patterns had predictive value. In this study, we used publically available data(ChIP-chip)for different types of histone modifications(methylation and acetylation) and for DNA methylation for Arabidopsis thaliana and then applied a machine learning based approach(a support vector machine) to demonstrate that patterns of these modifications are very different among different kinds of genomic feature categories(protein, RNA,pseudogene, and transposon elements). These patterns can be used to distinguish the types of genomic features.DNA methylation and H3K4me3 methylation emerged as features with most discriminative power. From our analysis on Arabidopsis, we were able to predict 33 novel genomic features, whose existence was also supported by analysis of RNA-seq experiments. In summary, we present a novel approach which can be used to discriminate/detect different categories of genomic features based upon their patterns of chromatin modification and DNA methylation.展开更多
In our previous studies, significant hypermethylation of the sirtuin 1(SIRT1) gene and demethylation of the b-amyloid precursor protein(APP) gene were found in patients with Alzheimer's disease(AD) compared wit...In our previous studies, significant hypermethylation of the sirtuin 1(SIRT1) gene and demethylation of the b-amyloid precursor protein(APP) gene were found in patients with Alzheimer's disease(AD) compared with the normal population. Moreover, the expression of SIRT1 was significantly decreased while that of APP was increased in AD patients. These results indicated a correlation of DNA methylation with gene expression levels in AD patients. To further investigate the epigenetic mechanism of gene modulation in AD, we used two epigenetic drugs, the DNA methylation inhibitor 5-aza-20-deoxycytidine(DAC) and the histone deacetylase inhibitor trichostatin A(TSA), to treat human neuroblastoma SK-N-SH cells in the presence of amyloid b-peptide Ab25-35(Ab25-35). We found that DAC and TSA had different effects on the expression trends of SIRT1 and APP in the cell model of amyloid toxicity. Although other genes, such as microtubule-associated protein s, presenilin 1, presenilin 2, and apolipoprotein E, were up-regulated after Ab25-35treatment, no significant differences were found after DAC and/or TSA treatment. These results support the evidence in AD patients and reveal a strong correlation of SIRT1/APP expression with DNA methylation and/or histone modification, which may help understand the pathogenesis of AD.展开更多
文摘The global incidence of depression is progressively on the rise and tends to occur more in younger generations,however the pathogenesis of the disease is unclear.Meanwhile,epigenetics is a modification which produces heritable alterations in the DNA sequence,which ultimately manifest in phenotypic differences.It has been suggested that the onset and development of depression can be tentatively explained by the combination of epigenetic and environmental factors.This paper reviews epigenetic changes in depression in the context of environmental factors,including DNA methylation modifications,histone modifications,and non-coding RNA regulation.An epigenetic-based therapeutic outlook was also proposed in this paper,which initially elucidates the epigenetic mechanisms underlying the pathogenesis of depressions and provides a theoretical basis for the treatment of depression.
基金supported by the National Science Foundation of USA(No.IIS 0916250)The University of Georgia Franklin College of Arts&Sciences research fund
文摘Dynamic regulation and packaging of genetic information is achieved by the organization of DNA into chromatin. Nucleosomal core histones, which form the basic repeating unit of chromatin, are subject to various post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitinylation. These modifications have effects on chromatin structure and, along with DNA methylation, regulate gene transcription.The goal of this study was to determine if patterns in modifications were related to different categories of genomic features, and, if so, if the patterns had predictive value. In this study, we used publically available data(ChIP-chip)for different types of histone modifications(methylation and acetylation) and for DNA methylation for Arabidopsis thaliana and then applied a machine learning based approach(a support vector machine) to demonstrate that patterns of these modifications are very different among different kinds of genomic feature categories(protein, RNA,pseudogene, and transposon elements). These patterns can be used to distinguish the types of genomic features.DNA methylation and H3K4me3 methylation emerged as features with most discriminative power. From our analysis on Arabidopsis, we were able to predict 33 novel genomic features, whose existence was also supported by analysis of RNA-seq experiments. In summary, we present a novel approach which can be used to discriminate/detect different categories of genomic features based upon their patterns of chromatin modification and DNA methylation.
基金supported by the National Basic Research Development Program of China (2006cb500700)the National Natural Science Foundation of China (30470904 and 31401627)+3 种基金Guangdong Provincial Natural Science Foundation of China (2010B031600070 and 2015A030313066)Science and Technology Social Development Project of Guangdong Province (2008B030301320 and 2012B031800053)a Guangdong Provincial Science and Technology Project (2013B051000009)a Guangzhou Science and Technology Plan Application Basic Research Project (2012J410076)
文摘In our previous studies, significant hypermethylation of the sirtuin 1(SIRT1) gene and demethylation of the b-amyloid precursor protein(APP) gene were found in patients with Alzheimer's disease(AD) compared with the normal population. Moreover, the expression of SIRT1 was significantly decreased while that of APP was increased in AD patients. These results indicated a correlation of DNA methylation with gene expression levels in AD patients. To further investigate the epigenetic mechanism of gene modulation in AD, we used two epigenetic drugs, the DNA methylation inhibitor 5-aza-20-deoxycytidine(DAC) and the histone deacetylase inhibitor trichostatin A(TSA), to treat human neuroblastoma SK-N-SH cells in the presence of amyloid b-peptide Ab25-35(Ab25-35). We found that DAC and TSA had different effects on the expression trends of SIRT1 and APP in the cell model of amyloid toxicity. Although other genes, such as microtubule-associated protein s, presenilin 1, presenilin 2, and apolipoprotein E, were up-regulated after Ab25-35treatment, no significant differences were found after DAC and/or TSA treatment. These results support the evidence in AD patients and reveal a strong correlation of SIRT1/APP expression with DNA methylation and/or histone modification, which may help understand the pathogenesis of AD.